Chapter 07: Developing Clinical Research Initiatives: Challenging Surgical Conventions
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Description
Dr. Sawaya explains that Dr. Fred Lang established the infrastructure for the research program in the Department of Neurosurgery. He describes the types of questions that the Department’s research projects investigate. He next discusses the Department’s controversial study of surgery performed on patients with multiple brain metastases, a taboo intervention according to conventional surgical wisdom. The Department performed a retrospective investigation of data which then went to a randomized trial documenting the effectiveness of the procedure. Dr. Sawaya contributed to these studies and the findings that changed therapy nationally.
Dr. Sawaya briefly speaks about his work with lasers, then explains a surgical probe that uses a GPS system to establish its location. He discusses the many challenges that tumors present and some of the technology used to determine tumor location and size. He stresses the importance of learning much more about brain anatomy.
Identifier
SawayaR_02_20130625_C07
Publication Date
6-25-2013
City
Houston, Texas
Interview Session
Topics Covered
The University of Texas MD Anderson Cancer Center - Building the InstitutionMD Anderson Impact; Ethics; Healing, Hope, and the Promise of Research; Discovery, Creativity and Innovation; Research, Care, and Education in Transition; Career and Accomplishments; The Researcher; Discovery and Success; MD Anderson Impact; Technology and R&D; Overview; Definitions, Explanations, Translations; Professional Practice; The Professional at Work
Transcript
Tacey Ann Rosolowski, PhD:
I guess the evolution of the actual services, the variety of services that were provided to patients under the umbrella of neurosurgery. Am I correct in that?
Raymond Sawaya, MD:
Well, that’s part of this clinical research. We have research, we have a laboratory, and we have clinicals. It was essential that we have the infrastructure to conduct clinical trials.
Tacey Ann Rosolowski, PhD:
So what was that—tell me how that was set in place?
Raymond Sawaya, MD:
This is what I gave to Fred Lang. Fred, with the research nurses and Dr. Suki’s managerial help, established the backbone and the infrastructure for the clinical research program. And there we had monthly meetings for concept of what it is that we want to test. What is the question? We are not a drug development department. We are a surgical department. So we were more interested in things that can be tested through surgical approaches. One example was, if you have a brain metastases, is it better treated through surgery, removing it? Or is it equally well or better treated through focused radiation, which is called stereotactic radiation? And so we had a randomized study that Fred led that compared surgery versus radiosurgery for the management of brain metastases. That’s an ideal question to be handled by a surgical department with collaboration of our radiation oncologists. And we did that.
Tacey Ann Rosolowski, PhD:
What other kinds of questions like that were managed?
Raymond Sawaya, MD:
Seizures—patients with brain tumors may have seizures. The standard of care in the country was to give everybody that has brain surgery medicine to prevent seizures. Well, is that necessary? Those drugs are not necessarily safe. They can cause reactions and complications. So with Fred, we established a randomized trial where we randomized patients who were having brain surgery or who we were cutting through the brain to receiving or not receiving anticonvulsants, and that trial was completed. And it actually was published a couple months ago showing that there is no need to give them automatically. So that changes the standard of care that has been established through no particular science but more fear than science. That, “Oh, they could have a seizure. Let’s give them this medicine to prevent seizures.”
Tacey Ann Rosolowski, PhD:
I’ve talked with a number of people about the view that a lot of people at MD Anderson had at least up into the ‘80s of sort of the suspicion of randomized trials maybe for ethical reasons or a sense that it wasn’t really necessary.
Raymond Sawaya, MD:
Yeah, that’s a very good point. When I presented the concept to the clinical research committee of randomizing patients with multiple brain metastases, that’s another study that I did here early on. I published a paper in 1993 on the role of surgery for multiple brain metastases. Now this was taboo. This was contraindicated at the time. If you said, “I have a patient with multiple metastases. I’m going to operate on them.” They would say, “Whoa, no way.”
Tacey Ann Rosolowski, PhD:
Why?
Raymond Sawaya, MD:
Because the idea is that obviously you cannot successfully treat them.
Tacey Ann Rosolowski, PhD:
You mean cutting in multiple places at the same time?
Raymond Sawaya, MD:
And I did. And I published that paper in 1993. That paper single-handedly has taken me all over the world. It’s truly amazing. One paper, because it was so out of the ordinary, it was so novel that it became a landmark paper. But it was based on retrospective data. It wasn’t prospective studies. So I said, “Well, to give it more meaning, let’s do a randomized study. Prospective.” Well, I was told by some people, they said, “Well, that’s not ethical. Why don’t you operate on all of them? Why do you want to randomize them?” See what I mean?
Tacey Ann Rosolowski, PhD:
Absolutely. But you felt confident based on the retrospective studies.
Raymond Sawaya, MD:
Because it was controversial that I thought if I do a randomized study I would garner more support for the idea. As it turned out, that one paper, even retrospective, has changed the thinking through the country about patients who have more than one metastasis in their brain.
Tacey Ann Rosolowski, PhD:
Now, as you selected your patient population, did they have a single sort of brain metastasis?
Raymond Sawaya, MD:
No.
Tacey Ann Rosolowski, PhD:
Okay. And not a single sort of surgery either?
Raymond Sawaya, MD:
No. Surgery is fairly common, but the origin of the cancer comes from multiple different organs. The most common is lung, then breast, then melanoma, then kidney, then colon. Those are the five leading causes of brain metastases. But lung and breast are by far the most common, just because they are so much more common as diseases by themselves. So we would lump all these five types together as brain metastases. Remember, this was early ‘90s. Since then, we have evolved into looking at each specific type of cancer with brain metastases separately, like melanoma. Skin cancer is a very special disease by itself. So now we’re looking more at each histology separately. But the surgery technique is the same.
Tacey Ann Rosolowski, PhD:
I see. Okay. So you weren’t testing—
Raymond Sawaya, MD:
Except we’re testing the en bloc versus piecemeal. There it made some tremendous differences. Really, really tremendous.
Tacey Ann Rosolowski, PhD:
That’s very interesting. In the minutes that we have left, just so we maybe are looking at some focused questions so we can use our time well. I wanted to ask you to tell me about some of the different surgical techniques that you brought into the department. Because I read that when you were recruited to come, one of the reasons was your expertise in laser surgery. So could you talk to me a bit about the technique that you brought to the institution?
Raymond Sawaya, MD:
It really didn’t materialize. I did publish a book on lasers in neurosurgery very early on in Cincinnati but really didn’t turn out to be a long-lasting contribution. So I’m looking for the book, and I’m sure I have it here somewhere.
Tacey Ann Rosolowski, PhD:
Could you describe to me exactly what laser surgery does?
Raymond Sawaya, MD:
Well, laser is supposed to be a non-touch, no-touch, technique. So you have a probe and you have a laser which is a light that comes out of that probe. So if I want to laze this arm on this watch, I would point the laser on it and then step on a pedal, and it will specifically burn and evaporate this arm. So think of that. You have a tumor that is this small, and there is a nerve on the left, and there is an artery on the right. If you use gross tools, you could damage one or the other just by manipulating. By not touching these two structures and pointing the laser right on the tumor, and then burning it slowly— You paint—you know?
Tacey Ann Rosolowski, PhD:
Right. So I gather that the light point is much, much smaller than an—
Raymond Sawaya, MD:
It is.
Tacey Ann Rosolowski, PhD:
Okay. But on the other hand—
Raymond Sawaya, MD:
But the problem is it’s too small. It’s not efficient.
Tacey Ann Rosolowski, PhD:
Right, and hands shake.
Raymond Sawaya, MD:
Yeah, you could stabilize it with an arm. But that laser can hit the artery too, and you end up with a hole in the artery. So there were downsides to it, but mostly it’s just that it was just too slow. It was just not efficient.
Tacey Ann Rosolowski, PhD:
Interesting. So what replaced it?
Raymond Sawaya, MD:
What replaced it is better magnification, better tools to magnify that. A much improved MRI scan, so that we could see the tracks now where they are, the tracks that go down next to the tumor.
Tacey Ann Rosolowski, PhD:
And the tracks meaning?
Raymond Sawaya, MD:
The track meaning the cables that connect the neurons in the brain and hand or the finger and the arm .There is a cable that you do not see when you are looking in there. You see white matter; it’s not specific. But now the MRI will color it in blue and as we see the scan—as we’re operating, we have a probe that has GPS on it that will show you on the screen where the tip of your probe is. That brings us to the 2006 Brainsuite. You probably read about the Brainsuite.
Tacey Ann Rosolowski, PhD:
I have it written down on my list of things, but before I ask you that question, I wanted to ask you maybe something that’s even more basic, which is what are the real challenges that brain tumors present to a surgeon?
Raymond Sawaya, MD:
We don’t have x-ray vision, so we don’t know where the margin or the border is of the tumor. And if you don’t know where the border of the tumor is, then how do you know whether you have reached that border or whether you have exceeded that border? So clearly that’s one problem. Another problem is we don’t know by just looking at the brain which part of the brain is critical and which part of the brain is not critical, which part of the brain you can cut through and which part of the brain you cannot cut through. So that also is important to have the right tools that are showing us where those cables are or small blood vessels are. And where’s the limit of the tumor, vis-à-vis of those cables. Because you can go all the way to the edge of the tumor, but you cannot go past the edge; otherwise, you end up with a lot of complications. Here is a picture of the brain suite that you can have if you want.
Tacey Ann Rosolowski, PhD:
The Brainsuite. Thank you, great. Absolutely, from the Brain and Spine Center—and I’m also thinking about the amazing challenge of when you insert something, what can you safely insert it through?
Raymond Sawaya, MD:
It depends on the size of that something. A tiny probe, we can insert through any part of the brain and nothing will happen. But if you have larger probes, then that’s riskier. But through mapping and MRI tractography, we are now learning so much more about the specific anatomy of a given brain than we could ever do before.
Tacey Ann Rosolowski, PhD:
That means an individual person’s brain, because I imagine there are differences.
Raymond Sawaya, MD:
Absolutely, and we do functional MRIs. So now we are stimulating certain areas of the brain and we’re imaging that on the MRI—language being one of them. Because language centers move a lot from patient to patient, so we cannot predict with any certainty where a specific language center is in a given person.
Tacey Ann Rosolowski, PhD:
Interesting, which is obviously key for preserving that individual’s function.
Raymond Sawaya, MD:
That’s why we frequently do awake craniotomies. We published an important paper on the technique and what to expect when you operate on these patients when they are awake.
Tacey Ann Rosolowski, PhD:
Well, why don’t we close there for today? Sounds like a good stopping place, and we can resume next time—give you time to get to your meeting.
Raymond Sawaya, MD:
Happy to. Thank you very much.
Tacey Ann Rosolowski, PhD:
Thank you. It was a lot of fun.
Raymond Sawaya, MD:
All right. Well I hope this is providing you with the right kind of information you need.
Tacey Ann Rosolowski, PhD:
Absolutely. So Dr. Sawaya, thank you very much. And I am turning off the recorder at 3:22. (End of Audio 2 Session 1)
Recommended Citation
Sawaya, Raymond MD and Rosolowski, Tacey A. PhD, "Chapter 07: Developing Clinical Research Initiatives: Challenging Surgical Conventions" (2013). Interview Chapters. 1543.
https://openworks.mdanderson.org/mchv_interviewchapters/1543
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